Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative Proteinopathies

The olfactory bulb (OB) shows early neuropathological hallmarks in numerous neurodegenerative diseases, for example, in Alzheimer's disease (AD) and Parkinson's disease (PD). The glomerular and granular cell layer of the OB is characterized by preserved cellular plasticity in the adult brain. In turn, alterations of this cellular plasticity are related to neuroinflammation such as microglia activation, implicated in the pathogenesis of AD and PD, as well as frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1) expressing microglia in the glomerular and granular cell layer, and the olfactory tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies (PDD/DLB), and FTLD compared to age-matched controls. The number of Iba1 and CD68 positive microglia associated with enlarged amoeboid microglia was increased particularly in AD, to a lesser extent in FTLD and PDD/DLB as well, while the proportion of proliferating microglia was not altered. In addition, cells expressing the immature neuronal marker polysialylated neural cell adhesion molecule (PSA-NCAM) were increased in the glomerular layer of PDD/DLB and FTLD cases only. These findings provide novel and detailed insights into differential levels of microglia activation in the OB of neurodegenerative diseases.

[1]  Houeto Jean-Luc.  [Parkinson's disease]. , 2022, La Revue du praticien.

[2]  A. Sasaki.  Microglia and brain macrophages: An update , 2017, Neuropathology : official journal of the Japanese Society of Neuropathology.

[3]  W. Streit,et al.  Microglia in dementia with Lewy bodies , 2016, Brain, Behavior, and Immunity.

[4]  J. O'Connor,et al.  Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis. , 2016, Stem cells and development.

[5]  Paul Edison,et al.  Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease. , 2015, Brain : a journal of neurology.

[6]  Christer Halldin,et al.  Effect of the myeloperoxidase inhibitor AZD3241 on microglia: a PET study in Parkinson's disease. , 2015, Brain : a journal of neurology.

[7]  L. Lue,et al.  Immune phenotypes of microglia in human neurodegenerative disease: challenges to detecting microglial polarization in human brains , 2015, Alzheimer's Research & Therapy.

[8]  C. Duyckaerts,et al.  TDP-43 Pathology Progression Along the Olfactory Pathway as a Possible Substrate for Olfactory Impairment in Amyotrophic Lateral Sclerosis , 2015, Journal of neuropathology and experimental neurology.

[9]  D. Gomez-Nicola,et al.  Post-mortem analysis of neuroinflammatory changes in human Alzheimer’s disease , 2015, Alzheimer's Research & Therapy.

[10]  E. Perry,et al.  Stage-Specific Changes in Neurogenic and Glial Markers in Alzheimer’s Disease , 2015, Biological Psychiatry.

[11]  O. Garaschuk,et al.  Neuroinflammation in Alzheimer's disease , 2015, The Lancet Neurology.

[12]  F. de Chaumont,et al.  Adult Neurogenesis Restores Dopaminergic Neuronal Loss in the Olfactory Bulb , 2014, The Journal of Neuroscience.

[13]  S. Rollinson,et al.  Patterns of microglial cell activation in frontotemporal lobar degeneration , 2014, Neuropathology and applied neurobiology.

[14]  P. Lucassen,et al.  Hippocampal Proliferation Is Increased in Presymptomatic Parkinson's Disease and due to Microglia , 2014, Neural plasticity.

[15]  P. Lucassen,et al.  Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients , 2014, Acta Neuropathologica Communications.

[16]  J. Molinuevo,et al.  TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis , 2014, Science Translational Medicine.

[17]  Alexander Gerhard,et al.  Frontotemporal dementia and its subtypes: a genome-wide association study , 2014, The Lancet Neurology.

[18]  J. Laczó,et al.  Odor Identification in Frontotemporal Lobar Degeneration Subtypes , 2014, American journal of Alzheimer's disease and other dementias.

[19]  V. Perry,et al.  Microglial priming in neurodegenerative disease , 2014, Nature Reviews Neurology.

[20]  J. Bol,et al.  Increased Amoeboid Microglial Density in the Olfactory Bulb of Parkinson's and Alzheimer's Patients , 2014, Brain pathology.

[21]  K. Jellinger,et al.  Olfactory bulb involvement in neurodegenerative diseases , 2014, Acta Neuropathologica.

[22]  B. Giros,et al.  Morphometric characterization of microglial phenotypes in human cerebral cortex , 2014, Journal of Neuroinflammation.

[23]  Nick C Fox,et al.  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease , 2013, Nature Genetics.

[24]  Hagen B. Huttner,et al.  Dynamics of Hippocampal Neurogenesis in Adult Humans , 2013, Cell.

[25]  V. Perry,et al.  Regulation of Microglial Proliferation during Chronic Neurodegeneration , 2013, The Journal of Neuroscience.

[26]  N. Hattori,et al.  Neuropathologic analysis of Lewy‐related α‐synucleinopathy in olfactory mucosa , 2013, Neuropathology : official journal of the Japanese Society of Neuropathology.

[27]  J. Winkler,et al.  Adult neurogenesis in Parkinson’s disease , 2013, Cellular and Molecular Life Sciences.

[28]  J. Nacher,et al.  Structural Plasticity of Interneurons in the Adult Brain: Role of PSA-NCAM and Implications for Psychiatric Disorders , 2013, Neurochemical Research.

[29]  F. Gage,et al.  Role of α-Synuclein in Adult Neurogenesis and Neuronal Maturation in the Dentate Gyrus , 2012, The Journal of Neuroscience.

[30]  M. Chesselet,et al.  Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein , 2012, Experimental Neurology.

[31]  H. Berendse,et al.  Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease , 2012, Progress in Neurobiology.

[32]  Richard L. Doty,et al.  Olfaction in Parkinson's disease and related disorders , 2012, Neurobiology of Disease.

[33]  S. Bernard,et al.  The Age of Olfactory Bulb Neurons in Humans , 2012, Neuron.

[34]  N. Torquet,et al.  Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb , 2012, The Journal of Neuroscience.

[35]  Fang Liu,et al.  Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain , 2011, Cell Research.

[36]  E. Hol,et al.  The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain. , 2011, Brain : a journal of neurology.

[37]  M. Babizhayev,et al.  Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care. , 2011, Current clinical pharmacology.

[38]  Mitchel S. Berger,et al.  Corridors of Migrating Neurons in Human Brain and Their Decline during Infancy , 2011, Nature.

[39]  M. Luquin,et al.  Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders , 2011, Acta Neuropathologica.

[40]  G. Enikolopov,et al.  Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. , 2010, Cell stem cell.

[41]  F. Calon,et al.  Widespread deficits in adult neurogenesis precede plaque and tangle formation in the 3xTg mouse model of Alzheimer’s disease , 2010, The European journal of neuroscience.

[42]  T. Hortobágyi,et al.  Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degeneration. , 2010, Brain : a journal of neurology.

[43]  E. Aronica,et al.  Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients , 2010, Neuropharmacology.

[44]  H. Payami,et al.  The heritability of risk and age at onset of Parkinson's disease after accounting for known genetic risk factors , 2010, Journal of Human Genetics.

[45]  H. Neumann,et al.  Alleviation of Neurotoxicity by Microglial Human Siglec-11 , 2010, The Journal of Neuroscience.

[46]  Fabia Febbraro,et al.  Microglia Acquire Distinct Activation Profiles Depending on the Degree of α-Synuclein Neuropathology in a rAAV Based Model of Parkinson's Disease , 2010, PloS one.

[47]  E. Masliah,et al.  Mutant α-synuclein exacerbates age-related decrease of neurogenesis , 2008, Neurobiology of Aging.

[48]  C. Tanner,et al.  Association of olfactory dysfunction with risk for future Parkinson's disease , 2008, Annals of neurology.

[49]  Jane S. Paulsen,et al.  Detection of Huntington’s disease decades before diagnosis: the Predict-HD study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[50]  B. Ritz,et al.  Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease , 2007, Neurology.

[51]  P. Eriksson,et al.  Response to Comment on "Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension" , 2007, Science.

[52]  J. Relton,et al.  Neuroinflammation in Parkinson’s patients and MPTP-treated mice is not restricted to the nigrostriatal system: Microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb , 2007, Experimental Gerontology.

[53]  Alexander Hammers,et al.  In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease , 2006, Neurobiology of Disease.

[54]  Elizabeth L Sampson,et al.  In vivo detection of microglial activation in frontotemporal dementia , 2004, Annals of neurology.

[55]  H. Berendse,et al.  Idiopathic hyposmia as a preclinical sign of Parkinson's disease , 2004, Annals of neurology.

[56]  Charles Duyckaerts,et al.  Dopamine depletion impairs precursor cell proliferation in Parkinson disease , 2004, Nature Neuroscience.

[57]  D. Dickson,et al.  Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein ɛ4 , 2003 .

[58]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[59]  P. Rakić,et al.  The generation, migration, and differentiation of olfactory neurons in the adult primate brain , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Nigel J. Cairns,et al.  Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages , 2001, Neuroreport.

[61]  K. Marder,et al.  Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. , 2000, The American journal of psychiatry.

[62]  P. Hoogland,et al.  Tyrosine hydroxylase immunoreactive structures in the aged human olfactory bulb and olfactory peduncle , 1999, Journal of Chemical Neuroanatomy.

[63]  Geoffrey A. Donnan,et al.  Activated Macrophages and Microglia Induce Dopaminergic Sprouting in the Injured Striatum and Express Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor , 1999, The Journal of Neuroscience.

[64]  F. Gage,et al.  Neurogenesis in the adult human hippocampus , 1998, Nature Medicine.

[65]  T. Kosaka,et al.  How simple is the organization of the olfactory glomerulus?: the heterogeneity of so-called periglomerular cells , 1998, Neuroscience Research.

[66]  F. Maxfield,et al.  Microglial Cells Internalize Aggregates of the Alzheimer's Disease Amyloid β-Protein Via a Scavenger Receptor , 1996, Neuron.

[67]  Arturo Alvarez-Buylla,et al.  Chain Migration of Neuronal Precursors , 1996, Science.

[68]  S. Gordon,et al.  Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli [published erratum appears in J Exp Med 1992 Jan 1;175(1):309] , 1991, The Journal of experimental medicine.

[69]  J. Grafman,et al.  Olfactory function in corticobasal syndrome and frontotemporal dementia. , 2009, Archives of neurology.

[70]  仙石 錬平.  Incidence and extent of Lewy body-related α-synucleinopathy in aging human olfactory bulb , 2008 .